Search JIM Advanced Search

Journal of Chinese Integrative Medicine ›› 2008, Vol. 6 ›› Issue (6): 626-631.doi: 10.3736/jcim20080616

• Original Experimental Research • Previous Articles     Next Articles

Effects of Xiehuo Bushen Decoction on survival and differentiation of transplanted neural stem cells in brains of rats with intracerebral hemorrhage

Peng-cheng Zhong, Xing-qun Li(), Qing-hua Liang, Wen-fang Luo, Qing-er Liu, Jie-kun Luo, Tao Tang, Yuan Lin   

  1. Department of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, China
  • Received:2007-09-29 Online:2008-06-20 Published:2008-06-15
  • Contact: LI Xing-qun

Objective: To investigate the effects of Xiehuo Bushen Decoction (XHBSD), a compound Chinese herbal medicine, on the survival and differentiation of transplanted neural stem cells (NSCs) in brains of rats with intracerebral hemorrhage, and to explore the mechanism of Xiehuo Bushen formula in promoting the survival of transplanted NSCs.
Methods: NSCs separated from hippocampuses of neonatal SD rats were cultured. Sixty-five panel reactive antibody (PRA) positive SD rats were selected by lymphocytotoxicity methods. The PRA positive rats were made into intracerebral hemorrhagic model and divided into three groups: cerebral hemorrhage group (n=15), NSCs transplanted group (n=25) and XHBSD group (n=25). XHBSD was orally administered after 5-bromodeoxyuridine (BrdU)-marked NSCs were transplanted in brains of rats with intracerebral hemorrhage in the XHBSD group. Rats in the other two groups were administered distilled water. The expressions of interferon gamma (IFN-γ) and interleukin-4 (IL-4) mRNAs were measured by reverse transcription polymerase chain reaction (RT-PCR); the numbers of BrdU and 200 kD neurofilament (NF200) positive cells were detected by double-labeling immunofluorescence method.
Results: The expression of IFN-γ mRNA was down-regulated significantly in the XHBSD group, but the expression of IL-4 mRNA was up-regulated significantly (P<0.05). The numbers of BrdU and NF200 positive cells were also increased remarkably in the XHBSD group.
Conclusion: XHBSD can promote the survival and differentiation of transplanted NSCs, which may be related to inducing the expression of IL-4 mRNA and inhibiting the expression of IFN-γ mRNA.

Key words: Xiehuo Bushen Decoction, neural stem cells, interferon gamma, interleukin-4, rats

CLC Number: 

  • R289.5

Figure 1

Nestin positive NSCs (Immunofluorescence staining, ×400)"

Figure 2

BrdU positive NSCs (Immunofluorescence staining, ×400)"

Figure 3

Caesar red staining positive lymphocytes (Inverted microscope, ×100) PRA value is about 80%. "

Figure 4

Expression of IFN-γ mRNA in XHBSD group at different time points"

Figure 5

Expression of IL-4 mRNA in XHBSD group at different time points"

Table 1

Expressions of IFN-γ and IL-4 mRNAs 2, 4 and 7 days after transplantation ($\bar{x}$±s)"

Group n IFN-γ mRNA IL-4 mRNA
2 days 4 days 7 days 2 days 4 days 7 days
Cerebral hemorrhage 15 0.73±0.01 0.65±0.01 0.63±0.03 0.91±0.12 0.92±0.02 0.94±0.13
NSCs transplanted 25 0.80±0.21* 0.67±0.02 0.65±0.12* 0.90±0.02* 0.89±0.11 0.90±0.05*
XHBSD 25 0.68±0.01** 0.63±0.01 0.59±0.01** 0.96±0.02 0.97±0.03 0.99±0.01*

Figure 6

BrdU and NF200 positive cells in XHBSD group and NSCs transplanted group 21 d after transplantation (Double immunofluorescent labeled staining, ×400) A: XHBSD group; B: NSCs transplanted group"

[1] Zhao CH. The principle, technology and clinic of stem cells[M]. Beijing: Chemical Industry Press, 2005: 112
赵春华 . 干细胞原理、技术与临床[M]. 北京: 化学工业出版社, 2005: 112
[2] Drukker M, Katz G, Urbach A , et al. Characterization of the expression of MHC proteins in human embryonic stem cells[J]. Proc Natl Acad Sci U S A, 2002,99(15):9864-9869
doi: 10.1073/pnas.142298299 pmid: 12114532
[3] Ostenfeld T, Caldwell MA, Prowse KR , et al. Human neural precursor cells express low levels of telomerase in vitro and show diminishing cell proliferation with extensive axonal outgrowth following transplantation[J]. Exp Neurol, 2000,164(1):215-226
doi: 10.1006/exnr.2000.7427
[4] Hu SH, Wu H, Liu AQ . The immunological characteristics of central nervous system and the problem of immunological rejection of neural stem cell transplantation[J]. Guo Ji Nao Xue Guan Bing Za Zhi, 2006,14(7):547-551
doi: 10.3760/cma.j.issn.1673-4165.2006.07.013
胡苏华, 武衡, 刘爱群 . 中枢神经系统的免疫学特性与神经干细胞移植的免疫排斥问题[J]. 国际脑血管病杂志, 2006,14(7):547-551
doi: 10.3760/cma.j.issn.1673-4165.2006.07.013
[5] Yang F, Wan Q . The problem in the clinical application of cell transplantation therapy[J]. Lin Chuang Shen Jing Bing Xue Za Zhi, 2006,19(2):158-159
杨芬, 万琪 . 细胞移植治疗临床应用所面临的问题[J]. 临床神经病学杂志, 2006,19(2):158-159
[6] Obata F, Yoshida K, Ohkubo M , et al. Contribution of CD4+ and CD8+ T cells and interferon-gamma to the progress of chronic rejection of kidney allografts: the Th1 response mediates both acute and chronic rejection[J]. Transpl Immunol, 2005,14(1):21-25
doi: 10.1016/j.trim.2004.11.003
[7] He XY, Verma N, Chen J , et al. IL-5 prolongs allograft survival by down regulating IL-2 and IFN-gamma cytokines[J]. Transplant Proc, 2001,33(1):703-704
doi: 10.1016/S0041-1345(00)02212-0 pmid: 11267027
[8] Ray J, Peterson DA, Schinstine M , et al. Proliferation, differentiation, and long-term culture of primary hippocampal neuron[J]. Proc Natl Acad Sci U S A, 1993,90(8):3602-3606
doi: 10.1073/pnas.90.8.3602 pmid: 8475109
[9] Duquesnoy RJ, Marrari M . Multilaboratory evaluation of serum analysis for HLA antibody and crossmatch reactivity by lymphocytotoxicity methods[J]. Arch Pathol Lab Med, 2003,127(2):149-156
[10] Hooper DK, Hawkins JA, Fuller TC , et al. Panel-reactive antibodies late after allograft implantation in children[J]. Ann Thorac Surg, 2005,79(2):641-644
doi: 10.1016/j.athoracsur.2004.07.052 pmid: 15680851
[11] Rosenberg GA, Mun-Bryce S, Wesley M , et al. Collagenase induced intracerebral hemorrhage in rats[J]. Stroke, 1990,21(5):801-807
doi: 10.1161/01.STR.21.5.801 pmid: 2160142
[12] Nonaka M, Yoshikawa M, Nishimura F , et al. Intraventricular transplantation of embryonic stem cell-derived neural stem cells in intracerebral hemorrhage rats[J]. Neurol Res, 2004,26(3):265-272
doi: 10.1179/016164104225014049
[13] Tang T, Li XQ, Wu H , et al. Activation of endogenous neural stem cells in experimental intracerebral hemorrhagic rat brains[J]. Chin Med J (Engl), 2004,117(9):1342-1347
doi: 10.1370/afm.226 pmid: 1537742622
[14] Kim JY, Kim D, Choi I , et al. MHC expression in a human adult stem cell line and its down-regulation by hCMV US gene transfection[J]. Int J Biochem Cell Biol, 2005,37(1):69-78
doi: 10.1016/j.biocel.2004.04.024
[15] Kuwatani M, Ikarashi Y, Iizuka A , et al. Modulation of acute graft-versus-host disease and chimerism after adoptive transfer of in vitro-expanded invariant Valpha14 natural killer T cells[J]. Immunol Lett, 2006,106(1):82-90
doi: 10.1016/j.imlet.2006.05.001
[16] Zhou GY. Principles of immunology[M]. Shanghai: Shanghai Scientific and Technical Literature Press, 2000: 155
周光炎 . 免疫学原理[M]. 上海: 上海科学技术文献出版社, 2000: 155
[1] Bing-rong Li, Shi-yun Shao, Long Yuan, Ru Jia, Jian Sun, Qing Ji, Hua Sui, Li-hong Zhou, Yi Zhang, Hui Liu, Qi Li, Yan Wang, Bi-meng Zhang. Effects of mild moxibustion on intestinal microbiome and NLRP3 inflammasome in rats with 5-fluorouracil-induced intestinal mucositis. Journal of Integrative Medicine, 2021, 19(2): 144-157.
[2] Sitthichai Iamsaard, Supatcharee Arun, Jaturon Burawat, Supataechasit Yannasithinon, Saranya Tongpan, Sudtida Bunsueb, Natthapol Lapyuneyong, Pannawat Choowong-in, Nareelak Tangsrisakda, Chadaporn Chaimontri, Wannisa Sukhorum. Evaluation of antioxidant capacity and reproductive toxicity of aqueous extract of Thai Mucuna pruriens seeds. Journal of Integrative Medicine, 2020, 18(3): 265-273.
[3] Morufu Eyitayo Balogun, Elizabeth Enohnyaket Besong, Jacinta Nkechi Obimma, Ogochukwu Sophia Mbamalu, Fankou Serges Athanase Djobissie. Protective roles of Vigna subterranea (Bambara nut) in rats with aspirin-induced gastric mucosal injury. Journal of Integrative Medicine, 2018, 16(5): 342-349.
[4] Lucky Legbosi Nwidu, Raphael Ellis Teme. Hot aqueous leaf extract of Lasianthera africana (Icacinaceae) attenuates rifampicin-isoniazid-induced hepatotoxicity. Journal of Integrative Medicine, 2018, 16(4): 263-272.
[5] Kylie Connolly, Douglas Jackson, Candice Pullen, Andrew Fenning. Alpha-adrenoceptor antagonism by Crassostrea gigas oyster extract inhibits noradrenaline-induced vascular contraction in Wistar rats. Journal of Integrative Medicine, 2015, 13(3): 194-200.
[6] Udhaya Lavinya Baskaran, Sherry Joseph Martin, Rasool Mahaboobkhan, Sabina Evan Prince. Protective role of Triphala, an Indian traditional herbal formulation, against the nephrotoxic effects of bromobenzene in Wistar albino rats. Journal of Integrative Medicine, 2015, 13(2): 115-121.
[7] Hussein O. B. Oloyede, Matthew C. Adaja, Taofeek O. Ajiboye, Musa O. Salawu. Anti-ulcerogenic activity of aqueous extract of Carica papaya seed on indomethacin-induced peptic ulcer in male albino rats. Journal of Integrative Medicine, 2015, 13(2): 105-114.
[8] Anirudha A. Lande, Shirishkumar D. Ambavade, Uma S. Swami, Prafulla P. Adkara Prashant D. Ambavade, Arun B. Waghamare. Saponins isolated from roots of Chlorophytum borivilianum reduce acute and chronic inflammation and histone deacetylase. Journal of Integrative Medicine, 2015, 13(1): 25-33.
[9] Elizabeth Abidemi Balogun, Sylvia Orume Malomo, Joseph Oluwatope Adebayo, Ahmed Adebayo Ishola, Ayodele Olufemi Soladoye, Lawrence Aderemi Olatunji, Olatunji Matthew Kolawole, Stephen Olubunmi Oguntoye, Abiola Samuel Babatunde, Oluwole Busayo Akinola . In vivo antimalarial activity and toxicological effects of methanolic extract of Cocos nucifera (Dwarf red variety) husk fibre. Journal of Integrative Medicine, 2014, 12(6): 504-511.
[10] Urmila Aswar, Mayuri Gurav, Ganesh More, Khaled Rashed, Manoj Aswar. Effect of aqueous extract of Solanum xanthocarpum Schrad. & Wendl. on postmenopausal syndrome in ovariectomized rats. Journal of Integrative Medicine, 2014, 12(5): 439-446.
[11] Xin-fang Zhang, Ji Zhu, Wen-ye Geng, Shu-jun Zhao, Chuan-wei Jiang, Sheng-rong Cai, Miao Cheng, Chuan-yun Zhou, Zi-bing Liu. Electroacupuncture at Feishu (BL13) and Zusanli (ST36) down-regulates the expression of orexins and their receptors in rats with chronic obstructive pulmonary disease. Journal of Integrative Medicine, 2014, 12(5): 417-424.
[12] Benjamin Perry, Junzeng Zhang, Tarek Saleh, Yanwen Wang. Liuwei Dihuang, a traditional Chinese herbal formula, suppresses chronic inflammation and oxidative stress in obese rats. Journal of Integrative Medicine, 2014, 12(5): 447-454.
[13] Upendarrao Golla, Praveen Kumar Gajam, Solomon Sunder Bhimathati. Evaluation of diuretic and laxative activity of hydro-alcoholic extract of Desmostachya bipinnata (L.) Stapf in rats. Journal of Integrative Medicine, 2014, 12(4): 372-378.
[14] Qian Zhang, Xin-hua Xiao, Ming Li, Wen-hui Li, Miao Yu, Hua-bing Zhang, Fan Ping, Zhi-xin Wang, Jia Zheng ​. Chromium-containing traditional Chinese medicine, Tianmai Xiaoke Tablet improves blood glucose through activating insulin-signaling pathway and inhibiting PTP1B and PCK2 in diabetic rats. Journal of Integrative Medicine, 2014, 12(3): 162-170.
[15] Amir Rashidian​, Saeed Mehrzadi, Ali Reza Ghannadi, Parvin Mahzooni, Samira Sadr, Mohsen Minaiyan​. Protective effect of ginger volatile oil against acetic acid-induced colitis in rats: A light microscopic evaluation. Journal of Integrative Medicine, 2014, 12(2): 115-120.
Full text



[1] Dong Yang, Yong-ping Du, Qing Shen, Wei Chen, Yan Yu, Guang-lei Chen. Expression of alpha-smooth muscle actin in renal tubulointerstitium in patients with kidney collateral stasis. Journal of Chinese Integrative Medicine, 2008, 6(1): 41-44
[2] Hai-feng Wei, Bai-liu Ya, Ling Zhao, Cui-fei Ye, Li Zhang, Lin Li. Evaluation of tongue manifestation of blood stasis syndrome and its relationship with blood rheological disorder in a rat model of transient brain ischemia. Journal of Chinese Integrative Medicine, 2008, 6(1): 73-76
[3] Xi Lin, Jian-ping Liu. Herbal medicines for viral myocarditis. Journal of Chinese Integrative Medicine, 2008, 6(1): 76
[4] Xi Lin, Jian-ping Liu. Tai chi for treating rheumatoid arthritis. Journal of Chinese Integrative Medicine, 2008, 6(1): 82
[5] Liang-ping Hu, Hui Gao. Discrimination of errors in statistical analysis of medical papers published in the first issue of 2006 in Journal of Chinese Integrative Medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 98-106
[6] Yan-bo Zhu , Qi Wang, Cheng-yu Wu, Guo-ming Pang, Jian-xiong Zhao, Shi-lin Shen, Zhong-yuan Xia , Xue Yan . Logistic regression analysis on relationships between traditional Chinese medicine constitutional types and overweight or obesity. Journal of Chinese Integrative Medicine, 2010, 8(11): 1023-1035
[7] Wei Xu, Meng Shi, Jian-gang Liu, Cheng-long Wang . Collagen protein expressions in ischemic myocardium of rats with acute myocardial infarction and effects of qi-tonifying, yin-tonifying and blood-activating herbs and detoxifying and blood-activating herbs. Journal of Chinese Integrative Medicine, 2010, 8(11): 1041-1047
[8] Tao Wang , Feng Qin. Effects of Chinese herbal medicine Xiaoyao Powder on monoamine neurotransmitters in hippocampus of rats with postpartum depression. Journal of Chinese Integrative Medicine, 2010, 8(11): 1075-1079
[9] Ying Xu , Chang-chun Zeng , Xiu-yu Cai , Rong-ping Guo , Guang Nie , Ying Jin. Chromaticity and optical spectrum colorimetry of the tongue color in different syndromes of primary hepatic carcinoma. Journal of Chinese Integrative Medicine, 2012, 10(11): 1263-1271
[10] Xiang-ying Mao , Qin Bian , Zi-yin Shen. Analysis of the osteogenetic effects exerted on mesenchymal stem cell strain C3H10T1/2 by icariin via MAPK signaling pathway in vitro. Journal of Chinese Integrative Medicine, 2012, 10(11): 1272-1278